Alli from
Switzerland discovered the autism benefits of Bio Gaia Gastrus.
This
probiotic contains two different bacteria:-
· Lactobacillus reuteri 17938 (Lactobacillus reuteri Protectis)
· Lactobacillus reuteri ATCC PTA 6475
These two bacteria
have different effects.
The first
bacteria is very well researched and recently was shown to increase oxytocin in autism mouse studies. It is available on its
own and this is the product most people I know are using.
The second
bacteria is included in Bio Gaia Gastrus specifically for its additional anti-inflammatory
effects.
Recent
comments on this blog have shown that some people have a negative “histamine-y" reaction to Bio Gaia Gastrus. This is
entirely logical since the mode of action of the second bacteria is to generate
histamine to activate H2 receptors in the gut.
This might sound rather odd since histamine is thought
of as inflammatory, but the researchers working for Bio Gaia have shown that histamine
can produce the opposite effect, suppressing TNF
via Modulation of PKA and ERK Signaling.
Beneficial microbes and
probiotic species, such as Lactobacillus reuteri, produce
biologically active compounds that can modulate host mucosal immunity.
Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A
combined metabolomics and bacterial genetics strategy was utilized to identify
small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic
interaction liquid chromatography-high performance liquid chromatography
(HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC
fraction composition was determined by NMR and mass spectrometry analyses.
Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions.
Histamine is produced from L-histidine via histidine decarboxylase by some
fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the
histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of
histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory
factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using
Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed
TNF production via activation of the H2receptor. Histamine from L. reuteri 6475 stimulated increased levels of
cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A
(PKA) and resulted in suppression of TNF production by transcriptional
regulation. In summary,
a component of the gut microbiome, L. reuteri, is able to convert a dietary component,
L-histidine, into an immunoregulatory signal, histamine, which suppresses
pro-inflammatory TNF production. The identification of bacterial
bioactive metabolites and their corresponding mechanisms of action with respect
to immunomodulation may lead to improved anti-inflammatory strategies for
chronic immune-mediated diseases.
This may mean that people who respond well to H2 histamine
antagonists (Zantac, Tagamet etc) are unlikely to benefit from Lactobacillus.
reuteri ATCC PTA
6475.
It might also mean that people who respond negatively to Bio
Gaia Gastrus might get benefit from H2 histamine antagonists.
It might be worthwhile people trialing the single bacteria Bio
Gaia product (Protectis), if they have a negative reaction to Gastrus.
Thanks Peter, this answers a question I have just been trying to resolve.
ReplyDeleteIt is in line with what I can see in my son.
Despite his confirmed mast cell activation, H2-blockers had no effect in him in the past. I don't know why.
BioGaia Gastrus is able to control his mast-cell related flare-ups, I could check it twice in last months. It happens only with the use of 4-5 tablets/day as Alli suggested. Lower dose or BioGaia Protectis is not enough. B. Protectis might have other beneficial effects which I have yet to see if these are really related to L reuteri/oxytocin or just to being on holidays itself.
High dose of BG resulted in huge decrease in stimming/OCD in my son, this is really good to see and he is also more happy about this. Nothing helped for stuttering.
Do you think that it would be a good idea to try H2-blocker first if someone wants to trial BioGaia Gastrus - in order to avoid unpleasant histamine-related reactions and check the effects of H2 antagonist itself?
I also found allergen information from BioGaia, which I couldn't access on holidays. They claim that neither milk protein nor lactose are detectable in BioGaia finished products and gluten level is below <20 ppm, so can be labelled gluten-free. Specifically they mention use of milk in the culture for BioGaia Protectis tablets only and it seems like they don’t use milk at all to produce BioGaia Gastrus and BioGaia Drops. My son is allergic to milk and gluten, used all three without issues. I also wrote to Vivomixx and according to their reply it can be safely used in milk protein allergy, which is a good new as the previous version of this probiotic (VSL#3) couldn’t.
Agnieszka, I am sure if you could gather details of the all children who responded negatively, you could figure it all out. But you tend to hear only "snippets" of information.
DeleteI was thinking that perhaps histamine intolerance is the problem. Quite a few people told me they cannot use sodium benzoate or cinnamon because they know they have an issue degrading histamine, this is a known genetic dysfunction. Sodium benzoate is a DAO inhibitor and DAO is needed to degrade histamine.
It would be useful to know if people who cannot tolerate Gastrus, can tolerate Protectis.
It is all rather guesswork, but clearly if you want to trial Gastrus, start with just one tablet and then pause for a couple of days, or even just take half a tablet.
H2 antagonists are OTC in many countries and it is a good idea for people to check whether they give a beneficial effect. A small percentage of people with an autism diagnosis do indeed seem to benefit, but most do not.
Peter, what we tried with negative effects was Biogaia Protectis drops, Lactobacillus reuteri DSM 17938 (L. reuteri ProtectisTM).
DeleteI wonder if it was too strong a reaction to the bacteria itself and a problem with the resolution phase of the inflammatory process (as happens frequently with normal colds and childhood stuff that can linger for several weeks with him).
Jane.
Jane, in this paper
Deletehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794487/
it says
"Indeed, we have previously shown a low but detectable histamine production by L. reuteri DSM 17938"
referring to this paper
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799733/
So maybe the problem you experienced is also histamine. Stay clear from Gastrus.
Indeed. Lesson learned with this one.
DeletePeter, to add another "snippet" about my son: he never seemed histamine intolerant to me, didn't seem to have any problem with pickles, fermented foods etc and his blood DAO level was normal.
DeleteCould bad reaction to B. Gastrus mean it's worth to check histamine intolerance and consider a trial of low histamine diet, which some people with histamine intolerance regard as very helpful?
Agnieszka, I think the key to everyone's personalized autism treatment is to investigate all "odd" reactions they notice and try to figure them out. So a negative reaction to a generally very well tolerated product (Biogaia) should ring some bells. As you say it might very well be histamine intolerance and this should be investigated. If it is not histamine it must be something else and quite possibly that other cause might tell you something very useful to improve that person's well being.
DeleteSome diets are very time consuming and stressful. There is a large possible placebo effect, because if you make a big effort with diet you will really want to see a positive impact and most parents would far rather use diet than drugs.
They normally suggest an elimination diet to diagnose histamine intolerance. You could of course do the opposite and increase histamine and expect a quick negative effect, that is what I would do.
If it was me, I would also give an H2 blocker and expect to see some positive effect. I did previously check if my son responds behaviorally to H2 blockers and, like your son, he does not.
People assume allergies and mast cell issues are associated with histamine intolerance, but this does not seem to be the case.
I've checked low histamine diet and learned we already have it in place, because between son going GFCF and daughter's anaphylaxis with industrialized meats and seasonings, we are already there and didn't knew it.
DeleteAlso I've seen mention of Acetylcisteine as DAO inhibitor, and as such to be avoided (regarding histamine intolerance) BUT its a must for us, and I intend to keep it. But this makes me wonder about other interactions.
Maybe for some NAC + Biogaia should be avoided?
Are responders to Biogaia already using anti-histamines? I remember Alli is using Ibudilast, wouldn't this make the histamine from Biogaia (or other sources) a non issue???
Jane, the second bacteria in Gastrus is the anti-inflammatory one. People with a dysfunction immune system might have allergy, asthma, arthritis, IBS, IBD. Many of those people might be using antihistamines. But there are people with an underactive immune system, the ones who catch every bug going around and take a long time to recovery; those people you would expect to do poorly with Gastus.
DeleteIbudilast, like Montelukast is used for asthma and allergy, but it would not block the release of histamine directly. I think Alli said she used Ibudilast for flare-ups only.
It may be something else other than histamine that causes the problem, perhaps he has some unusual allergies, that you are unaware of. You can be allergic to almost anything. Your daughter has an unusual allergy.
Jane you done a Niacin flush test to see if there is actually a histamine problem and not something else?
DeleteAlso, you may have already tried DAO enzymes (the one we used was from Swanson's) which I think was more or less pig kidney extract (we have not used it in a while as the big red ears and cheeks have not shown up in a while now).
Hi Peter and Tyler, thank you for your replies.
DeleteHis immune system is certainly odd, it seems inefficient as he gets sick easily and for longer times, but I'm not sure about under/over active as he shows signs of both. (maybe some regulation is not working as it should, I don't know...)
Tyler, I've considered niacin flush sometime ago but ended up abandoning the idea. I've found an article saying the flush was not due to histamines but prostaglandins, so I wasn't sure it would work.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779993/#b45
I wasn't aware that we could supplement DAO enzymes...I'll look into it.
Cheers,
Jane.
Very interesting. This may be very random, but if one's child is a strong responder to benadryl for sleeping, would this product have a beneficial effect? Sleep onset is a problem, and don't want my child to take benadryl regularly but wondering if this creates changes in gut to help or hurt (or not have an effect). just starting yesterday
ReplyDeleteBenadryl sends you to sleep because it is a centrally acting (crosses into the brain) H1 histamine antagonist. It only works for a few days and then the pro-sleep will reduce as the H1 receptors get used to it. Melatonin is what seems to work for many people with autism who have sleep problems.
DeleteI doubt Biogaia will have a significant sleep effect, but it should not make it worse.
Be careful with long-term use of benadryl for ASD as :
Delete1. it is a reasonably strong anticholergenic compound and we typically like more acetylcholine (see Galantimine studies). As it blocks the acetylcholine sites ppl tend to feel quite unpleasant as they are reactivated when weaned off too..
2. is a DAO inhibitor, reducing metabolism of antihistamines, although that should also reduce Glutamate?
3. iirc benadryl also has an effect of storing up histamine in the mast cells and then releasing it when it stops being taken..
Also worth noting is that you should always give Biogaia in the morning as TNF-a has a role in sleep regulation: http://www.ncbi.nlm.nih.gov/pubmed/9917875
Finally, a side note that may be of interest.
In some children benadryl makes them hyper. Part of this is maturity, but some are cytochrome P450 (CYP) 2D6 enzyme ultra-metabolisers (http://www.ncbi.nlm.nih.gov/pubmed/18227744)
CYP2D6 is a pretty important enzyme in processing all sorts of drugs, for example it converts codeine into morphine :) Ultra metabolisers thus can get paradoxical or very odd effects from them..
With regards to giving Biogaia in the morning (Mossy), I have yet to see any information as to how long Biogaia stays in the digestive tract or more importantly how long it stays in the digestive tract as probiotics in general are considered to be transient guests along the way. I give my son Biogaia at night before bed, and he sleeps through the night and is now no longer peeing the bed (he is 7 years old). He could of just aged out of this problem, or it could be the result of some other intervention, but he has gone from me having to wake him up at least once during night to go to the bathroom so that he does not pee the bed, to not peeing the bed without my intervention (I could just be on a long lucky streak the last week or two but I never thought I would ever see this happen), and this improvement seems to have happened about the time I started giving him Biogaia Gastrus after culturing it in previously boiled milk for a day in a mason jar.
DeleteSo Mossy I guess the question for all of us here is when does Biogaia actually start working in the digestive tract after dosing (i.e. how many hours). If I give it to him at night and it takes a while to pass through and work its magic, it might be that it is at its most active in the very early morning when most REM stage sleep occurs.
From reading the comments here at least some of the reaction to Biogaia appears to be immediate. Looking at how probiotics work I'd imagine some would be longer-term too, particularly once you hit the maintenance dosage?
DeleteGreat to hear it appears to have regulated the sleep and bed issues, maybe due to overall lowering of inflammation or some other mechanism :)
So many pathways each of these interventions targets, someone somewhere must have built something you can just plug em into and it balances everything out..
HI Mossy, Tyler et al-
DeleteThanks for comments. I don't think it has regulated the sleep issues for my child yet but only a short time with the Gastrus. It is a sleep onset issues as it takes a while to go to sleep. My child has a movement disorder or chorea (not stimming so NAC or something like that has not been useful) and am wondering given that if you have thoughts. melatonin has not been very effective. One of the doctors recommended Lorazepam, but not great either, and it has its own issues (not the lower dose clonazepam) Benadryl is effective, but don't want to take it continually for the reasons discussed. Other thoughts would be appreciated. Fitbit has been good for learning about sleep as well as too much :(
Low doses of Mirtazapine (3-5mg) seem to have a long term sleep effect, that does not fade after a few days. At high doses this is used as an antidepressant, but at low doses you get the H1 histamine driven sleep effect. It also seems to have other beneficial effects in some people with autism.
DeleteAnonymous, as I am sure you well know hyperkinesia/dyskinesia is a common symptom in Huntingtin's disease. In Parkinson's disease, hypokinesia (sort of the opposite of dyskinesia/hyperkinesia). Hypokinesia in Parkinson's is the result of dopamine signaling no longer occurring due to the death of dopamine producing neurons in the ventral tegmental area. This causes a part of the basal ganglia system called the global pallidus externus to not send inhibitory messages to another part of the basal ganglia system called the subthalamic nucleus which acts like a reverse gas pedal on inhibiting part of the brain (the thalamus) that sends messages to the motor cortex. In Huntingtin's you have a situation where the main input areas to the basal ganglia system (caudate nucleus and putamen which are really the same brain area except they are separated by some white matter in humans) are atrophied causing this inhibitory action selection process to go awry because whenever you execute a movement (normally) the basal ganglia system must also suppress similar movements (so you select the right movement). If this is not working, you can have uncontrollable flailing of the limbs.
DeleteIn autism, the caudate nucleus has been shown to be physically enlarged in many people while the cells are not very compact. This means the caudate is not functioning properly just like in Huntingtin's disease (where the caudate is atrophied). So interventions that are going to help with chorea/tics are likely going to involve something dopaminergic without affecting mental function too much with the brute force approach via strong GABAergics like Lorazepam. Unfortunately, the dopaminergic options like Risperidone give us parents the YIKES! factor with all of their side effects. So the problem could be structural problems with the caudate/putamen or else there is just too much dopamine signaling occurring (boosting serotonin sometimes reduces dopamine production so that is another avenue of exploration).
Also, a paper I read just a few days ago showed that suppressing the dopamine output of the VTA is important in inducing sleep:
https://www.sciencedaily.com/releases/2016/09/160905114515.htm
so it looks like your goal here is to reduce environmental stimuli that helps generate dopamine and maybe even look at dietary restrictions on tyrosine/phenylalanine too (I am no expert in this so do your own research).
A few things which stimulate dopamine release that you might want to restrict at least 3 hours before bedtime:
(1) Exercise
(2) Caffeine
(3) Blue light (install smart LED's bulbs in house and go with red or green light in the evenings or just restrict all artificial light altogether).
@Anonymous
DeleteFor what it's worth, my daughter has a fairly strong response to benadryl as well and I haven't observed any changes in sleep with Gastrus. The one effect that 2 tablets a day seemed to have on her was that she seemed to become more tolerant of things she'd normally throw a fit about (e.g. someone blow-drying her hair after being in the pool). I'm not sure this can be attributed to the probiotic, but it's plausible enough so to me it's worth a shot.
On a related note, I've observed that hydroxyzine (another 1st gen antihistamine) works just as well as benadryl at getting/keeping her asleep, and I haven't seen any evidence that she's becoming desensitized to it after 6 weeks of use. So that may also be worth consideration in your case, if not for chronic use then just for nights when you're especially desperate to induce some zzz's.
Christopher
Low dose mirtazapine has an adavantage of not having anticholinergic effects as compared to Benadryl.
DeleteAt really low dose mirtazapine seems to affect only H1 receptors, so if you look for sleep inducing central antihistamine and want to avoid other unwanted effects (in our case dry mouth on Benadryl and irritability on drugs blocking 5-HT receptors) it may be a good choice in my opinion.
I suspect that it could also help those children who get paradoxically hyperactive on Benadryl or Hydroxyzine.
It is well explained in a blog by a person calling himself "The Last Psychiatrist":
http://thelastpsychiatrist.com/2009/01/treating_insomnia_with_less.html
Or just in this picture:
http://thelastpsychiatrist.com/images/remeron.JPG
I wonder if someone used low dose Mirtazapine for sleep or other reasons? Would appreciate to hear more about this drug in practice.
I'd be careful of mirtazapine as it has a far longer half life than other "sleep" meds (20-40 hours)
DeleteI think an interesting approach for those that have a histamine reaction with Biogaia may be combining it with a histamine regulating bacteria like Bifido Infantis/Longum or L Planetarium..
Mossy, for the first 2-3 weeks there is some drowsiness to mid morning, then it fares away. The improved sleep is maintained. In some people they benefit from behavioral changes unrelated to sleep. In theory it might give cognitive improvement, but had no effect in our case.
DeleteThe improved/prolonged sleep conitinued after cessation in our case, as if we had reset what was normal. For people with major sleep issues I think it is worth looking at. We do not have a big issue with sleep, my son is just an early riser, but it is always light outside when he wants to get up.
Now that is interesting.
DeleteIf the effects are maintained after cessation that could indicate a secondary effect beyond brain H1 impact? Some sort of circadian normalization perhaps..
First off, let me say I use Biogaia unconventionally in that I ferment it in boiled skim milk and then cool the milk down to room temperature before putting a tablet of Biogaia Gastrus in a mason jar and then letting it culture a day before feeding it to my son and daughter (less severe autism, but some socialization stuff I thought the oxytocin might help her with, not to mention he appetite which oxytocin can help with as well). I do this to increase the yield and decrease the cost which is very high at about 10 dollars a day between them. Since I am experienced with making kefir, I figured I would try this method and see what happens and anecdotally I have seen a lot of the improvements others have mentioned.
ReplyDeleteNevertheless, I have also noticed in my son only that he has recently started getting a lot of back acne (he is only age 7) since giving him Biogaia Gastrus using this method. Acne production is caused my many different things, but the immune system is obviously involved. I also recall reading that the 17938 strain not only increases oxytocin production, but also testosterone (which is associated with acne). The back acne has gotten a bit better with time and it could be because it is summer and he is outside sweating a lot, but I was wondering if anyone else has had this side effect or ideas about how this could be related to Biogaia Gastrus supplementation.
Tyler,
DeleteThanks for your thoughts on Biogaia Gastrus and testosterone. I have a son who will be 12 in 3 weeks so testosterone has become a big topic in our house. My son is obviously in the beginning stages of puberty so my observations need to be considered with that in mind. My son started getting pimples on his face coincidentally after we started BioGaia Gastrus this summer. He is also getting full erections (sorry to be graphic) all day long. We took a week off of the probiotic as it is recommended to give the body a break once in awhile. Yesterday my husband and I both remarked that the erections had diminished greatly. It never occurred to me that the BioGaia could be contributing. Again, it's hard to tease out what are normal adolescent changes and the increased oxytocin/testosterone. Thank you for sharing as I will continue to play detective with this.
--Christine
I gave my 9 year old NT son a dose of Gastrus and he broke out with the worst case of acne on his forehead...cleared within a week but I didn't give any more. He is also in "the T stage" and acne is becoming more common for him too, but the Gastrus definitely caused a flare. The 3 year old that I bought it for rejected the taste of the tablets altogether.
DeleteLreuteri does work for social engagement. We just ended up with the single strain drops for Mr. Pickyeater. I give 10 drops daily now, was doing 15. I may give the megadoses a try again in a few weeks but Tyler is right, it's quite an expensive probiotic.
:)
MKate
Peter, my son could have histamine intolerance as biogaia gastrus had a negative effect and it seems that nothing can fix his problem,could use l histidine as a supplement, as inhibits oxidative stress and tnf alpha il6 or would be worse in his situation? Valentina
ReplyDeleteValentina, the Biogaia bacteria cannot survive long in the gut, so its effect should naturally fade to zero. If histamine is the problem you could reduce its effect by blocking histamine receptors, for example with an OTC drug like Zantac.
DeleteAs me and my son are undermetylators,probably we could be more sensitive to histamines,this could be a piece of my son's puzzle that I was missing. My doubt with Zantac is that it reduces stomach acid which is necesary for fighting against bad bacteria.Valentina
DeleteValentina, after a week the Biogaia bacteria should have gone. Normally they talk about having good bacteria crowd-out the bad bacteria. So if you add a product to his diet full of good bacteria this might help.
DeleteIf try with an H1 antagonist like loratadine, think is the same as claritin, would help or must be an H2 antagonist?, sorry but this is complicated for me, I feel that because of histamine intolerance, he reacts negatively to probiotics or fermented food. Could use betaine hcl with Zantac or is better to use loratadine to help with his hyperactive behavoiur,ocd, giggling, sleep issues. Thanks for your help.Valentina
DeleteOk, will do things more simple, will try with loratadine, sorry for the questions, this is not a simple subject.Valentina
DeleteSince we are talking about histamine and allergic reactions, a paper came out today that showed how fat can influence mast cells in the digestive tract and what happens when the gut microbiome is cleared via antibiotics:
ReplyDeletehttps://www.sciencedaily.com/releases/2016/09/160908151248.htm
I know diet and autism has been a topic beaten to death for more than half a century now, but I found this research interesting in light of the fact many people with autism seem to "crave carbs" even though it could be that they are really just trying to "avoid fat".
Tyler, sorry to be on your back with all my commnts, its totally not intentional! :) We must be thinking along similar lines here. Below is a link to my holy grail, so to speak. I tried Vit E and Omegas a year ago aftr reading this paper but my son's apraxia didnt really improve. However, recently (last week) I reread and restarted Vit E and Omegas along with our new probiotic regimen. And he's been adding new words without prompting yesterday and today. Im convinced that the state of his digestion and gut previously (along with my ignorance at the time) were why the protocol failed last time and that these new pre, probiotics we are now using were the missing link. We also do fermented drinks now along with aloe distillate.
DeleteJust FYI :)
http://www.alternative-therapies.com/resources/web_pdfs/recent/0709_morris.pdf
MKate
Well yes if digestion is all messed up, many supplements will go to waste. You also need to pay attention to supplements that don't go well with others (when taken at the same time) because of interactions between them or competition for the same digestive enzymes necessary for absorption. For instance, calcium competes with many substances and EGCG from green tea extract will interfere with the absorption of iron (which can be a good thing if you are worried about your body getting too much iron from your diet).
DeleteHi Mkate,
DeleteAre you continuing with bumetanide as well? And are you still giving bioamicus or shifted to biogaia.
Your experience sharing will be much appreciated as I tried out omegas with my son as well when we started out in addition to entire array of vitamins, minerals a Nd digestives. But there was no marked improvement. Omegas and excess of vitamin a sometimes are known to cause excessive visual stimming which I think I observed in my son. I have come to understand now that syereotypies in my son are almost more marked when there have been issues of sleep, hunger and most importantly digestive issues..that is even after two bowel movements if something remains stuck inside, he will stare through corner of eyes which really is the only major odd expression concerning my son and I tell you it looks odd!
Wishes
Yes, he takes 1mg bumetanide but mostly it regulates his moods and sleep and he seems to have greater control over his muscles, more muscle energy. As for the oils, I think they are working better because of his gut being in better shape after a few weeks of pre,probiotics and quercetin. I use biocidin for any yeast symptoms (from quercetin) and sometimes Olive leaf extract which does help with gut issues and maybe immune health. Constipation was never a problem, it was usually loose BM before diet changes and probiotic regimen. Still using bioamicus, can't find biogaia drops at a reasonable price. May try gerber next.
DeleteTyler--You might have already discussed or come across this in research, but Amantadine is a non stimulant dopamine agonist that is used frequently for ADHD. I'm thinking of asking our pediatrician about it for my son, who also suffers from mild hyperkinesia and a few other hyperactive behaviors.
ReplyDeleteMKate
Well Amantadine could help normalize things if the problem is a receptor issue (which is why it is used to treat the side effects of long-term L-DOPA therapy in Parkinsons where chorea ends up becoming a problem), but it is kind of the opposite of what I was suggesting which was a dopamine antagonist or dopamine suppressant like Risperadone as if your child is displaying hyperactive chorea symptoms, it could be because of too much extracellular dopamine floating around (which has long been associated with autism severity and intellectual disability). In ADHD it has long been thought that the lack of dopamine signaling in the prefrontal cortex leads to the inability to focus which is why stimulants like amphetamine classically have been used to treat the condition, yet because of this reason ADHD treatments for hyperactivity often don't work in the autism patient pool or even make things a lot worse.
DeleteHyperactivity in general can occur for many other neurological reasons in different parts of the brain, though it is thought that chorea symptoms (uncontrolled flailing of the arms like a puppet) is because of a dysfunction or the caudate/putamen. The caudate/putamen inputs are glutamatergic (i.e. they respond to glutamate signaling), but many of their outputs (via the basal ganglia system) are dopaminergic (the in between stuff is mostly GABAergic as 95% of the neurons in the basal ganglia are GABAergic). So, it could be that the caudate/putamen could be erroneously functioning because of a glutamate receptor issue as well, rather than there simply being too much free glutamate in the brain causing excessive signaling.
I suspect a neurologist would have a pre-made list of different drugs to try until one of them happened to work since there is no real clear consensus at all on how the basal ganglia system is dysfunctional in autism at this time, especially since many different forms of autism could cause many different forms of dysfunction in the basal ganglia.
Parkinson's and Huntingtin's are far more homogenous in their symptoms than autism so that is why doctors have pre-baked solutions give to their clients. If I had your child, I would like into very mild dopamine antagonists and then go from there, but who knows maybe your kid would benefit from Amantadine.
Tyler,what would be a mild dopamine antagonist, not so weak? My son´s case is similar, like chorea movements and tics when excited, weaning off risperidone. Valentina
ReplyDeleteWell there are several non-prescription options for dopamine antagonism. One is melatonin that I recall when reading about its many effects. Of course just about everyone with a sleep-challenged autistic child probably already gives melatonin, but you could try a megadose (10 milligrams) which is what I do at the moment with my son. I would prefer not to give melatonin at all being that it is a powerful hormone that needs more long-term research on children, but sometimes you have to pick the lesser of two evils and children not sleeping is very bad for their behavior, cognitive function, and neural development.
DeleteThere are many dopamine antagonists:
https://en.wikipedia.org/wiki/Dopamine_antagonist
and I am no expert on their relative affinities, but many of those drugs on that list have a lot of side-effects.
I would try and at least eliminate all environmental stimulants of dopamine first (as much as possible). If your kid tolerates glasses, you can get blue light filtering glasses and see if that makes any difference (less blue light means less dopamine), or like I mentioned before get these lights:
http://bluetoothlightbulb.com/
then as bedtime approaches set them to a red setting (no blue light means the melanopsin receptors in the eyes won't be activated) and don't change the color setting until morning. Submarines traditionally would have red light so that the eyes would not have to readjust to darkness as when you popped out of the submarine at night when surfacing, the sailors eyes would not have to spend half an hour readjusting to darkness.
Tyler, Peter, what do you think about using domperidone as dopamine antagonist?would it be safe in small doses?, sorry, been writting few questions with no answear,is something wrong?valentina
DeleteValentina, dopamine antagonists are widely used by to treat schizophrenia and bipolar. These drugs do often have side effects. As Tyler pointed out, melatonin is a mild dopamine antagonist. Melatonin seems to be safe even at very large doses, it also has numerous other beneficial effects. It is also OTC.
DeleteThankyou Peter, yesterday read many dopamine antagonists , antipsychotics, antiemetics, herbs, and today got up with melatonin in my mind!. Now have your your answear! will increase the dose, he was taking 6 mg at bedtime but could be 3 mg in the morning and 6 mg at bedtime?valentina
DeleteValentina, I do not currently use melatonin, but I know some people are using doses of 20mg in autism. That would be best given before bedtime.
Deleteok, just read Tyler´s answear, thankyou for the explanation, think will start with 10 mg at bedtime.
DeletePeter, quick question for you: If melatonin given at a larger than recommended dose of around 5 mg (for a small child) produced wakefulness throughout the night, would a dopamine agonist be a better solution?
DeleteIt looks like a small percentage of people taking melatonin respond with wakefulness. There must be a clever explanation for this. It all depends what exactly is the problem, whether a dopamine agonist will help. Figuring out why melatonin gives the opposite effect might tell you something very useful to understand you subtype of autism.
DeleteHello Peter,
DeleteCould melatonin shorten the gap my son has to have between sleeps..around eight hours. This makes his sleep onset time at night around one thirty..two and he has to get up at seven in the morning which seems so unfair..it's pathetic to shovel cereal down his throat in his semi sleepy state. By four in noon he has to have a nap. I do not know a way out of this.
Kritika, your question is best answered by others who make regular use of melatonin. Ideally you would use nothing more than plenty of physical exercise to promote healthy sleep. Once you start giving substances to change sleep patterns there may well be negative as well as positive effects. So my view would be only to intervene when there is a big problem, in some cases sleep is a huge issue.
DeleteIn a minority of cases melatonin does not help and then you would have to find something else. My suggestion was very low dose mirtazapine for a few weeks. After a few weeks really good sleep, a new sleeping pattern may have been established that requires no further intervention.
Kritika, melatonin helps someone who needs rest to get sleep, but doesn't forcefully induces sleep. On the other hand, once someone sleeps with the aid of the extra melatonin the person feels tired if it is interrupted (after all she was in real need of rest to begin with).
DeleteIf possible you could try to advance his nap to 1 or 2 pm and give melatonin at night (30 minutes before bed time). Once the new sleep pattern is established, you can try to wean off melatonin if it bothers you.
With similar routine my kid now sleeps from 8:00pm to 6:00am, a down time is mandatory by 1:00pm, but he can choose to just slow down or have a nap, he takes the nap 2 or 3 times a week. Sometimes he still have nights of insomnia, but they are sparse enough (1 or 2 nights every 8 or 10 weeks) that I do not intervene further.
Note that once he starts resting at night and with aging he will need less and less the nap time.
Also if you allow the nap time by 4pm, even with melatonin he will likely not sleep at a reasonable time at night, because he will not be tired enough for it to have an effect. The same will likely happen if you try melatonin during the day (it will not be a nap, but profound sleep, so no need to sleep again until several hours later).
Regards,
Jane.
Hi Jane,
DeleteI get your point but we get home from the school and therapies only by two pm and it seems so cruel to keep him awake till 8 pm. Additionally, a requirement for minimum wakeful hours of eight hours means that if he gets up at seven, he just can't fall asleep by 2 or 3pm. Also, the nap gives him a fresh start in the evening and he can brush up what he learnt in his school hours. He is 4.5 and attends a mainstream school..two languages to learn to read and write, longhand apart from mathematics. But we are keeping our targets high..preparing for the worst but hoping for the best.
My son's problem is not insomnia or sleep quality..he is a deep sleeper. It's this need for a particular wakeful gap between consecutive sleeps that I wish I could alter somehow. I hope I have been able to convey my concerns.
I do not see a solution unless I do away with with the afternoon nap altogether on which case I will have to brace myself for a good five six hours of crankiness which under the present circumstances I am unwilling and probably unable to withstand. I do not know if low dose mitrazapine use can be helpful or really needed for fixing his sleep.
Kritika, I don't see either. Personally I wouldn't go for drugs where a change in routine would do. But its your choice to make.
DeleteMelatonin has different effects at different doses. In adults I believe the dosages are:
Delete0.1-0.3 milligrams (mini dose) shifts the circadian cycle forward so that sleepiness occurs earlier in the evening.
3 milligrams - Helps with sounder sleep so that you are less likely to awake. If you have problems with waking up in the middle of the night or if your child does (which is perfectly normal, though inconvenient with modern lifestyles), this dosage can help with that.
10 milligrams - Most people consider this a megadose. This is the dose you want for melatonin's antioxidant properties as brain inflammation can induce hyperactivity and cause someone to wake or even pee the bed.
50 milligrams - This is the dose you want to induce sleep, though you would probably be better served using other sleep aids as this is a lot of melatonin.
Also, with respect to sleep if you use a lower dose or a much higher dose, melatonin receptors are going to downregulate just as they do with GABAergics. Really, 10 milligrams is excessive for use in sleep except that melatonin has many other important properties.
Melatonin is well researched, so don't take my word for it here, just do a little light reading yourself. Try Googling "Melatonin Scientific Reviews" and read the studies yourself.
Tyler and Valentina- first Tyler: very interesting about blue light abd dopamine - this must explain why ipad use for typing and doing school work triggered meltdowns in my son. So perhaps this is a good path to explore with him - dopamine issues.. Valentina - my son sounds similar to yours in terms of this and histamine (he also has several homozygous mutations for DAO and HNMT). wondering if we could compare notes re: treatments? If interested please email me - tanyastatum@gmail.com
DeleteI realize that drugs are a last resort when it comes to sleep, as we want our kids to develop a healthy sleep/wake cycle naturally. As previously mentioned however, some kids are just never able to do it on their own. For those of you who have tried everything (like we had), you may want to try a very small dose of Clonidine (0.1mg). My son's doctor told us to try it and after 11 years of not sleeping, we finally found something that worked. Perhaps not for everyone, but those of you who are dangerously sleep deprived (like we were) will surely welcome any ideas.
ReplyDelete--Christine
Hi Christine,
DeleteWould you mind sharing your son's weight? Melatonin stopped working a few years ago, and we have sort of managed by tweaking sleep routines. Recently though, my daughter is simply unable to fall asleep, and even when she does, is sleeping very lightly, not entering deep sleep. She seems pretty fine though, in fact, is doing the best she has in a decade. She is making gains globally. I am the one who is knackered, and also the problem of scheduling classes, activities etc.
RG, SO sorry for the late reply. I had been sick all week and just got back to reading the blog. My son's weight is roughly 75lbs. The nice thing about Clonidine is that it doesn't cause a hangover effect in the morning. I completely understand how incredibly difficult it is when your child can't fall asleep. One other thing I do is rub pure essential oils on my son's ankles and the back of his neck. I use one from a company called doTERRA (serenity) -- you can buy it on Amazon. I know that may sound wacky to some, but it really does help and smells good too. I have also used Lemon Balm -- one dropper in a glass of water with a splash of lemonade is very calming. Just a few ideas in case you haven't tried them. Best of luck!!
Delete--Christine
In my grandson's case adrenal cortex supplement helped for good sleep. He would wake 3,4 or more times crying or screaming. He has to be put on the shoulder and phase the floor to go back to sleep. Sometimes he would be completely awake and be fresh and energetic around 3 am and will start to play with one of his parents. After an hour or two he will eat something and go back to sleep. From his 6th month to one year he was in India but his circadian rythem never got adjusted. He would go to sleep as per British time. His urine OAT test reavealed high catecholamine and high serotonin level. He also craved salt. So his nutritionist suggested adrenal cortex and his sleep improved and he slept through the night. But still he will be restless in his sleep some nights. Recently we added taurine and nowadays he goes to deep sleep. But taurine level was normal in his OAT.
DeleteChristine, Salempeacock, thank you so much for your feedback. I completely missed it and am only now seeing it. You see, except for the recent comments section on the right side of this blog, I have no idea how to track other comments.
DeleteThis site comments are very valuable to me. Usually I use online rssreader like feedbucket to track comments.
DeleteTry this link to see the comments:
http://feedbucket.com/?src=http%3A%2F%2Fepiphanyasd.blogspot.com%2Ffeeds%2Fcomments%2Fdefault%3Falt%3Drss
Hi Peter,
ReplyDeleteI know you have mentioned a very low dose of mirtazapine, and I wish I could try it. My concern is that it is contraindicated in seizures, and it is only in the last month that my daughter's seizures have become much more controlled, with just one (which is still one too many) a month, with all the other, smaller ones cleaned up. This is due to Diamox. I will write our experience with Diamox and low dose clonazepam in detail soon.
She has been having a spectacular month, its just this sleep issue that seems to have come hand in hand, though she seems unaffected by it. Would much appreciate your thoughts.
RG, the paper below reviews mirtazapine and seizures.
DeleteA key point to note is that while Mirtazapine has several known effects on different receptors, at very low doses it is really just affecting H1 histamine receptors. At higher doses it starts affecting all kinds of other things, to the extent that at high doses mirtazapine does not induce sleep.
The study below shows that in the rare cases, presumably at high doses, the seizure effect is entirely reversible.
I was crushing a 30mg tablet and then weighing with digital scales 6 doses of 5mg which I put in gelatin capsules.
I would talk to your doctor and also look at the link given by Agnieszka.
http://thelastpsychiatrist.com/2009/01/treating_insomnia_with_less.html
P-1116 - Seizures associated with mirtazapine: a case report and review of literature
http://www.sciencedirect.com/science/article/pii/S0924933812752835
"Mirtazapine was discontinued in the patient with no recurrence of seizures. A review of the literature revealed that seizures associated with Mirtazapine are exceedingly rare. In fact, Mirtazapine is recommended for use in patients with epilepsy due to its low epileptogenic potential."
Thank you Peter.
DeleteIs there a reason you chose 5mg rather than a lower one of say, 3mg? Was there a reason you tried mirtazapine, I didn't think Monty had sleep issues. And what were the reasons for stopping?
My hesitation with mirtazapine is the same as with Ketotifen. Apparently histamine is protective against seizures. Though in our case, in the past, horrible allergies themselves induced seizures.
RG, there are anecdotal reports that low doses of mirtazapine can have beneficial effects in some autism. There has been research into the possible cognitive enhancing effect of mirtazapine in schizophrenia, which biologically/genetically overlaps with some autism.
DeleteSince we already use allergy drugs it seemed worthwhile to see if low dose mirtazapine has cognitive effects in our case. If it did, I could look at substituting it for something currently used for allergy.
After a few weeks the morning drowsiness ceased, then I looked to see if there was any noticeable cognitive improvement. There was not, so I stopped.
I picked 5 mg as this dose has been used by others before, but you certainly could see if you get the sleep effect with 2 or 3 mg.
Peter, how many hours did the morning drowsiness last? There was no loss of cognition either?
DeleteWhen you stopped it, did you taper off?
I just returned from the endocrinologist who thinks the 50mg dose of Synthroid is probably responsible for the worsening of the sleep. He would like us to 'power through it' for another four weeks, by which time he expects it to go away.
He has also prescribed metformin for the monthly seizure.
Forgot to mention, the endocrinologist who is a mountain climber, and is familiar with Diamox in that regard, not in his practice, said that it seems likely that the synthroid and diamox are synergistic and can effect some good changes.
DeleteRG, what dose of Diamox are you using?
DeleteDid you trial intranasal insulin yet?
The drowsiness was noticed at school. He took the pill before bed, had extended sleep, woke up a bit drowsy and this lasted till about 11am. The drowsiness would mask any cognitive effect and in effect if you are drowsy you will not be on peak intellectual form. After 3 weeks the sleep remained extended, drowsiness had faded entirely, but no cognitive gain was evident. After cessation sleep remained extended.
http://www.ashg.org/2014meeting/abstracts/fulltext/f140122034.htm
DeleteRegarding diamox I came across this post. Interesting.
Salempeacock, very interesting. It is brief so here it is for everyone, particularly RG.
DeleteCombination Biotin Responsive Encephalopathy and Hemiplegic Migraine Disorder presenting as Autism and episodic limb dysfunction/seizures in a 10 year old girl. P. Benke Genetic Division, Joe Dimaggio Children's Hosp, Hollywood, FL.
A 10 year old girl presented to Genetic Clinic with findings of autism. She had all the features of autism, including developmental delay/late language and a paucity of verbal expression, poor understanding, poor social skills, poor eye contact and oppositional behaviors. Some improvement in her symptoms had been accomplished with a low gluten, dairy free diet, but she was still far behind an age appropriate level. Physical examination did not yield any clues, but when asked whether or not her hair and nails grow, her mother said that they did not. The mother was asked to observe hair and nail growth for 3 weeks; when it was observed that they did not grow, she was instructed to start 10 mg/day biotin, which resulted in good growth of both. In addition, there was immediate improvement in school performance. The child began to talk better and her memory dramatically improved. She was thought to have had partial seizures from age 2-3 yrs, with changes in her EEG. Antiepileptic medicines and the change in diet decreased, but did not completely eliminate the episodes, during which one or another limb would lose function, and she developed a concurrent inability to talk or communicate. She would recover after a few hours time. She improved and was free of the latter symptoms when she vacationed in Colorado, and took Diamox. She was then treated for presumptive hemiplegic migraine with Diamox, and dramatically improved. Her EEG normalized, and she began to demonstrate normal, even advanced artistic skills. Her school work improved further, with normal reading and math skills, and a gain in IQ scores. An Exon genome scan (GeneDx) demonstrated a new mutation (p.T364M, c.1091 C>T ) in the ATP1A2 associated Hemiplegic Migraine gene, not found in either parent, but did not show a mutation in a biotin dependent gene process. This study shows that 2 genetically unrelated disorders together can lead to a diagnosis of autism, and symptoms can improve dramatically when specific gene appropriate measures are employed.
Thank you Peter, Salempeacock. I think Agnieszka had pointed me towards this study earlier. The improvements I am seeing in my daughter are similar. I wish I could access the full paper to see the dosage that was used.
DeleteShe is on 125mg of Diamox split into two doses. I have not started the insulin yet, decided to do the Diamox first. Its right at the top of the list though. So very soon.
We started the low dose clonazepam first, at .025mg per day. Within three days, she developed better control over her diaphragm. She had been part of a music group where she would sing so softly to be not heard at all, even in front of a mic. Three days after starting the clonazepam, her group had a performance in front of a large audience, and there she was belting out the songs, to her teacher's and our amazement. From being nearly silent, she transformed into their lead singer. Since then, she has been able to maintain a strong singing voice and the last couple of months has been taking classical voice and doing well. She seems to enjoy practicing the scales and is singing songs like 'the water is wide' 'Michael row the boat ashore' etc. The other change was in yoga. She had had a few classes and the breathing part was alway tough. As well as shavasana which is relaxation in the supine position. She could never lie still for even a minute, unable to close her eyes or keep her fingers and body still. Right after the clonazepam, she began doing it for several minutes at a stretch, and within a couple of weeks was up to 15 minutes of lying still. She also began responding more readily to greetings and simple questions from people not close to her.
I started the Diamox right after she had a seizure just prior to beginning her monthly period. I wanted to see if it would prevent further seizures during this time. It did that. Within two weeks after that we were also able to take her on vacation involving several flights. She had been refusing to get on a plane for over two years, saying that her 'head bothers' like in seizures. She became much more aware and began paying sustained attention to things around her. She was also interacting just a little bit more with people. Handled the changes, transitions with ease. There was also an instance where we were visiting family and she was sitting in front with my brother who was driving, and I was at the very back of the suv. Her cousins were singing along with the radio and when they finished, they asked her if she could sing something. She sang 'Michael row the boat ashore' all by herself, clear as a bell, from the front. No prompting or support from anybody. We also noticed that on several occasions, such as when she had a stomach upset, and at other times such as on the airplane, she could stretch out on the sofa or seat, close her eyes and lips and lie still as in shavasana for an hour or more. Completely relax herself.
DeleteWhile we were away, she had a stomach upset with vomiting and by the next day she was out of ketosis. That, coupled with being close to her menstrual cycle, resulted in a seizure. It was a strange and somewhat unnerving one. It was a tonic only, not clonic, and her body arched, and for the minute that it lasted, her eyes were open and she was fully conscious throughout. She also immediately snapped out of it, no post ichtal phase at all. No motor weakness or confusion. Went straight back to whatever she was doing before. No irritability afterwards. The day after we came back home though she developed a sudden fever in the afternoon while napping and woke up to a febrile seizure. Again, it was only tonic, with no post ichtal or residual effects. Interestingly, for the first time, we had a positive fever effect that lasted for a week after. Her sleep completely normalized, she slept every day from around 10pm to 8am.
She also began communicating more. We were at the cinema, watching a movie, and there was a scene where the main character says that X is moving to the UK. Immediately, my daughter piped up, saying, "Heathrow airport. I want to go to Bath (which is where we used to live)". Then, " I want to go to Heathrow airport and go straight to V's house. Salisbury". V was a very good friend. Continued, " No Frimley, no C's house". Since then, speech has continued to improve. She is using more novel phrases, and is providing verbs on demand.
A month in, I began noticing a marked difference in reading and writing and comprehension. Her motor apraxia is no more, she is only lagging in motor skills due to lack of experience and practice. It took her two tries to master rolling her yoga mat. This was not something that would have even been possible for her earlier. She is also doing some pretty advanced yoga poses. She is learning by imitation and verbal prompts only, no physical prompts. Recently, I enrolled her in a Scratch programming class, fully expecting to be kicked out into an adjoining arts class instead. I was shocked to see her figure it all out, including saving her work at the end. Another amazing development was that she was so keen on the piano her music teacher used for singing scales, that we decided to try a few lessons. She has had only a few, but is able to pick out the notes, read the very basic first sheets and read and play at the same time. This was a kid whose fingers appeared almost spastic, rigid and extended. Could not separate her fingers.
DeleteHypotonia and a lack of energy that I thought might have been a mitochondrial dysfunction is 90% gone. She doesn't need to hold on to us while walking, and is able to walk around the stores without needing to sit down everywhere. In fact, I see the pre puberty kid again, full of beans, jumping around.
The effects are definitely cumulative, and continuing. There is no additional diuresis.
Thanks RG, very interesting.
DeleteOne thing I find interesting is that my son started singing after settling into 0.02mg Clonazepam daily after a week or two. We have tapered it down now to see the impact without and he still hums along.
One thing I would like to note re: Diamox is that the increased acidity might cause increased nausea and vomiting directly, a H2 agonist may help balance that out and one should probably ramp slowly.
Thank you Em. I have been watching the acidity because she is already on the MAD/Ketogenic diet. We had two episodes of vomiting about two weeks apart, both while in the toilet. Sorry for the tmi, but she has had no formed bowels for a while now, even before the Diamox. Also, every few days, continuous cramping and running to the toilet. She is due for a gastrointestinal workup soon.
DeleteIts likely a bacterial issue, because Culturelle helps with the cramping and sitting in the toilet for hours. It hasn't helped the usual, non diarrheic, loose stools though. She is on it most days.
On the topic of probiotics, wanted to mention that we are big fans of Culturelle here. I keep it in my handbag, and my husband in his computer bag. He travels a lot and it has been a lifesaver many times. It has twice shortened episodes of gastroenteritis. He recovered within a day.
DeleteFor those in the US, we buy it from Costco, 80 tabs for $20.
I forgot to mention a big change after the low dose clonazepam. My daughter had to have a mini psychological assessment as part of a state requirement for services. She had a great attitude, was very relaxed with the psychologist, and did some novel tasks very well, including marking answers on a large sheet that was 2' wide. We noticed that her visual agnosia was not evident. Though the tests were not comprehensive enough to be a full IQ test, the psychologist informed us that she did the cognitive parts very well and got them all correct.
DeleteTesting of any sort in the past, has been sheer torture. Suddenly, here we were.
Hello RG,
DeleteIt's so encouraging for us to hear the strides your daughter seems to be making.. congratulations to you. And its your insight, intellect and deep involvement with your child as a mother that is making all this possible. Of course, for you it's no big deal.
It would be helpful if you could share at what age you started your daughter on diamox and clonazepam and according to you which intervention gave you maximum cognitive enhancement. I believe your daughter is on bumetanide as well. Are you doing all these drugs in combination simultaneously. Diamox seems to have serious side effects ..how long do you plan to continue this.
In your daughters her hemiplegic migraines and probably seizures would obviously affect her functionality and in this regard diamox s benefits will outweigh it's side effects.
It would be kind of you if you could briefly respond to some of my questions.
Regards
Hi Kritika,
DeleteWe started the low dose clonazepam in June of this year and the Diamox in July.
We started the MAD/Ketogenic diet February 2014. Verapamil in May 2014. Bumetanide May 2015. Synthroid September 2015. Sytrinol December 2015. Low dose clonazepam June 2016. Diamox July 2016.
The others are Magnesium Taurate and Potassium citrate.
For us, Diamox has been the biggest one so far, for cognition, including speech. I cannot answer for sure if some of the change is due to the underlying stack. Verapamil, Bumetanide, low dose clonazepam, all improved cognition. With low dose clonazepam, her reading improved, as well as her pronunciation. With Diamox, auditory processing is much stronger, so she's able to listen carefully, comprehend better and respond.
Given that you don't have easy access to Bumetanide, Diamox might be a good starting point. Especially since I remember you mentioning that a bit of diuresis gives good benefit in your son.
Kritika, I can understand your being fearful of the side effects of many of these drugs. In my opinion, you have to be even more fearful of a poor prognosis in the event of future 'hits' and development of other comorbidities. Many of these are well studied, Peter is amazing in the amount of literature that he references in his posts. If one or some of them work that is a real chance you have now of changing the trajectory of your son's life.
My understanding is that most of these drugs are for life. There may be some additions and substitutions, but for the most part, they'll probably continue for the foreseeable future.
RG-Are you giving Bumetanide and Diamox, or have you switched to just Diamox? I am thinking of trying it as I suspect a large part of my son's communication issues are due to an auditory processing disorder. Have you seen any side effects from Diamox?
DeleteMKate
Woops, never mind! Just reread your posts RG, and see you are stacking both. :)
DeleteI am giving both. When we started Bumetanide, we got a good response with 1mg per day, one dose. I always thought of increasing but never got around to it.
DeleteThe 400mg Potassium citrate almost completely reduced the sound sensitivity, and the Diamox then seems to have stepped in with sustained attention and learning. I have posted our experience under the Potassium post.
The one effect that I noticed was an evening out of appetite. I wouldn't call it a reduction. My daughter loves her meat, especially a good steak, and tended to eat rather large portions, so could manage only two meals a day. Nothing in between, no snacks, drinks etc. Since Diamox, she is simply unable to eat beyond 6 to 7oz, and instead has added in a third meal of eggs.
We had two vomiting episodes, two weeks apart, the first one was about a month after starting Diamox, and I think it was due to a stomach upset. She had eaten some steak tartare the previous day. Em thought it might be the Diamox.
I hope tolerance doesn't build and I am trying to use this window of opportunity to take her baseline functioning to a higher level.
I thought it might increase susceptibility to nausea due to the increased acidity but lots of things can cause vomiting.
DeleteOut of curiousity how long did it take to build up an effect and how long does it take to "wash out" in your experience?
May be worth pulsing if tolerance is a fear.
The timeline has been different for various effects. Day 1 onwards no seizures, big or small. Within a few days was willing to go on a flight, in fact became quite eager to do so, where before she had refused. About a week in, I noticed that pronunciation was better. More self aware, comfortable in her own skin, if that makes sense. Translates to a confidence about herself. She used to appear shy, inhibited. That completely changed. Was quite willing to go off with her cousins, uncle etc. Did not keep looking around for me. Also managed to eat airplane food, preferred to eat a rubbery omelette and sausage than a packed meal from home. Two to three weeks in, she began commenting more on things around her, also using novel phrases instead of scripts. More readily coming in with verbs when requested. A month in, huge improvement in motor skills. Between month 1 and 2, apraxia almost completely gone. Acquiring motor skills very fast. Oh, month 1, she started piano. At the very first lesson, the teacher asked her to identify her five fingers by number, and she was able to separate them individually. She had not been able to do this before. Also able to follow some very basic sheet music, book 1 and 2 piano lessons. Its a very big thing for us because she has had visual agnosia and tracking has been difficult. I have always had to point with my finger for her to follow along. Month 2 much better auditory processing, followed by good comprehension. Also in the last month, she has become more playful, interacting more readily with others. She is also, for the first time since she regressed into autism, able to play tricks on us. Like saying she is going to the bathroom, while quickly going to her room to play a bit. Also, deliberately waiting for a class to start and then rushing off to the toilet. Arguing with her teacher about what she wants to do next. A couple of her teachers have said that she seems to be 'naughty' now. Thankfully, they say it with a smile, as we are all happy to see this side of her.
DeleteWe have missed a couple of doses here and there but its been ok. I would think washout would be similar to bumetanide, a few days perhaps?
Peter, Tyler,
ReplyDeleteI wanted to mention that Bumetanide at night is able to, somewhat mildly, induce sleep after about an hour. Interesting, since Tyler has the opposite effect.
We have this effect from bumetanide also. My son is 3 and usually ends up with a nap at around 2 or 3pm. Yet, interestingly, melatonin given at too high a dose seems to make him wake up throughout the night. (that was my question above about melatonin, I didn't sign my name though, apologies)
DeletePeter, gave 10 mg melatonin and produced wakefulness through the night, you know about my son's type of autism and his reactions to bio gaia, nac, etc, the fact that melatonin causes the opposite reaction, what would be showing about him? I am puzzled, he presents underactivated immune system, ocd,hyperactive and many movements.Valentina
ReplyDeleteWell different people have different sensitivities to melatonin as having a lot of melatonin in your brain won't do much if the the receptors are insensitive or few in number. Most of your melatonin receptors are in your gut. With respect to sleep, melatonin tends to increase REM sleep which is generally a good thing in sleep deprived people who tend to have an imbalance in NREM restorative sleep versus REM sleep. Both forms of sleep consolidate different types of memory so you don't want too much or too little of either. If your child is waking up from too much melatonin, it might be it is too much for them or else their brain has not downregulated the receptor count to match the dose. Remember there are many different reasons for giving melatonin, not just for sleep. I give the high dose for oxidative stress support at night as melatonin is a potent anti-oxidant, plus it tends to downregulate serotonin which tends to be too high in the body in those with autism and the brain inflammation from oxidative stress can cause restlessness on its own.
DeleteIf your child is waking up from 10mg melatonin it is because their receptors have not adjusted yet and you might have too much REM sleep (i.e. dreams/nightmares) that are occurring too early in the night and causing the child to wakeup.
If you are just trying to help with sleep issues, 3mg or less is probably what you want to do. Some people also have high levels of glutamate or at least an imbalance in the glutamate/GABA ratio in the brain that can cause sleeping issues as well.
You can also try ZMA (Zinc, Magnesium, Aspartate) which I give my son now after I got tired of home-brewing aspartic acid with baking soda. Many people take ZMA explicitly for sleeping problems. ZMA is not too expensive and may help more than melatonin does in your case. NOW Foods is the brand we currently use at the moment. You can find it on Amazon or just about any other online retailer.
Tyler, was looking for a dopamine antagonist rather than a sleep aid, he has been taking risperidone since he was 3, now he is 10 and think is time to leave it. Now he is on 5 drops, the weaning off process was very low but he has dyskinesias, tics and stereotypes, very obsessive and hyperactive, and he is peing the bed. Perhaps a dopamine antagonist is not what he is needing, what do you sugest? Is good idea leaving risperidone? Valentina
DeleteOne intervention that made the biggest difference in my son's hyperactivity was aspartic acid which I have posted about here before. The reasoning goes back to old and forgotten research concerning reducing opioid withdrawal symptoms in heroin addicts, and the opioid system has classically been one of the more invested areas of research in autism. So I would mix L-Aspartic Acid and Baking Soda together to yield monosodium aspartate which is salty but is dissolvable in water, while plain L-Aspartic Acid does not dissolve in water.
DeleteEventually, I switched to ZMA which is an old supplement with a complicated past that was originally used as a sports supplement for raising testosterone (there is a lot of controversy governing these claims), but others found ZMA to be very helpful as a sleep aid as zinc deficiency and magnesium deficiency are two of the most common mineral deficiencies in the western world these days as most people don't eat enough plants to get adequate amounts of them. If you don't have those mineral deficiencies then supplementing zinc and magnesium likely won't do much if anything, but just about everybody does nowadays unless you take a regular multivitamin that includes adequate levels of those minerals in a well absorbable form. For my purposes, I mostly just care about the aspartate in ZMA which by weight is about 80% aspartate.
The aspartate helped with the SIBing and hyperactivity immensely and switching to ZMA has not had any negative change in impact (prior to using ZMA I supplemented magnesium separately as magnesium citrate).
The recommended dose is 3 capsules a day for men and 2 capsules a day for women, but I do 2 capsules a day twice a day for my son, but if he was your son's age I would probably do 3 capsules twice a day or 2 capsules 3 times a day.
The point is that there could be many different things causing your son's symptoms (which are pretty much standard moderate to severe autism symptoms) and my previous post was just to explain the part of the brain that likely is not working properly that may cause some of those symptoms (chorea). General hyperactivity has been shown to be caused by many other areas being dysfunctional, especially some which are heavily connected with the basal ganglia such as the motor cortex of which morphological abnormalities have been found in multiple studies.
Another thing to consider is that dysfunction in the opioid receptors can drive dopaminergic dysfunctions (which is why heroin gets people "high"). In autism, it is thought in many cases there are receptor issues or else issues with endorphins (which is short for endogenous morphines) and is the original reasoning for the whole gluten-casein diet which I don't believe in personally, even though I think the original reasoning (i.e. dysfunctions in the opioid system likely being driven by HPA axis dysfunction) are a major contributor to autistic symptoms.
I would do 6 capsules a day of ZMA per day and see if it does anything for two weeks and then go from there. Either you will see a big effect (as I did) at that time, or else try something else.
Valentina, another area you can look into are mglur5 negative allosteric modulators:
Deletewhich have been heavily researched lately with respect to drug addiction and dyskinesia (hyperkinesia) in Parkinson's disease as well as a mouse model of autism:
https://www.researchgate.net/profile/Daniel_Smith40/publication/224856090_Silverman_JL_Smith_DG_Rizzo_SJ_Karras_MN_Turner_SM_Tolu_SS_Bryce_DK_Smith_DL_Fonseca_K_Ring_RH_Crawley_JN_Negative_allosteric_modulation_of_the_mGluR5_receptor_reduces_repetitive_behaviors_and_rescues/links/54cef1870cf29ca810fd2a5b.pdf
There are multiple avenues of research in normalizing activity in the basal ganglia (the dorsal striatum is defined as being the same thing as caudate and putamen) and toning down mglur5 activity is one of them.
There are to my knowledge no non-drug options for mglur5 NAM's but the above link provides a good review of some of the current available options and all but one:
https://en.wikipedia.org/wiki/Fenobam
that was listed under Wikipedia's page are either in phase II clinical trials (or at least as far as they got) or else for research purposes only.
Try to find strains that don't produce D-lactate. Lactic acid producing strains can have an effect on some children with autism. Not sure if it is short bowel syndrome or so many carbohydrates already producing lactic acid and then one gets too many. So how do you reduce the lactic acid production of this strain to attain its benefit without the side effects some get? Would culturing work?
ReplyDeleteThis artciel states that the second strain increases oxytocin yet here it states the first one does:
ReplyDeleteInterest in Lactobacillus reuteri grew after research confirmed that changing aspects of the digestive system can influence the immune system. A strain of Lactobacillus reuteri called ATCC PTA 6475 has been found to improve levels of testosterone and oxytocin, as well as skin quality in animal studies.
Just wondering which is correct?
It is quite possible that more than one bacteria causes an increase in oxytocin.
DeleteIn my son Lactobacillus reuteri 17938 (Lactobacillus reuteri Protectis), produces a change in emotional behavior consistent with an increase in oxytocin.
A different L.reuteri sold by a Canadian company called BioAmicus, appears to produce similar behaviors in humans.
PTA 6475 produces immuno-modulatory effects that seem to be of great benefit to some people with autism, but cause an immediate negative reaction in others.
Because PTA 6475 is only sold in a tablet together with L. reuteri 17938 we cannot say whether PTA 6475 raises oxytocin in humans, maybe it does. The combined tablet certainly can, at least in some people.
Taken off longecity discussion about L. Reuteri atcc6475:
ReplyDelete"In the past I have done something with microbiology. Knowing about stuff like growth curves, substrates, metabolites, buffers, pH control, osmotic stress, etc. could be useful if you want to grow bacteria. Go read a couple of microbiology books, read some relevant studies and patents if you really want to grow these bacteria. I may post some of my experiments in the future.
In a clinical trial they used 10 billion CFU daily of ATCC PTA 6475. If 100 million CFU would be sufficient, why would they give the women in the study daily 100 as much as in a Gastrus tablet? Seems to me that it requires more CFU to sort a significant systemic effect. Gastrus is meant as an adjunct treatment for those with H. pylori infections, targeting the GI tract. The reason why DSM 17938 is included in Gastrus is likely because it produces significantly more reuterin than ATCC PTA 6475.
The estimated study completion date is next month. The press release looks positive. Hopefully BioGaia considers to launch a single strain probiotic with ATCC PTA 6475 soon. If the product is lauched it will be likely a powder, just like in the clinical trial. BioGaia registered a new trademark this year, PROVESI. That could be it or it could be nothing relevant. Only time will tell."
Seems they used about 100 times as much atcc6475 than one tablet of gastrus in the study on women with regards to bone preservation!
Hope they release a product with far far more CFU in the future.
https://www.trademarkers.com/EUIPO/016422231/trademark-PROVESI-granted-to-biogaia-ab
You can ferment it in milk like I do to greatly increase the yield.
DeleteAny chance you could write a DIY lol, Ive seen people discuss this also on longecity and seems you gotta be a rocketscientist to understand what they are saying over there :/
DeletePeter, what if instead of excessive glutamate, there is actually too little, maybe particularly for those who respond badly to benzodiazepines?
ReplyDelete"Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate - serotonin interactions for pharmacotherapy."
https://www.ncbi.nlm.nih.gov/pubmed/9720980
Can you see any relevance? Would foods high in glutamic acid for a week or so be an easy intervention to draw conclusions?
Petra, people who respond badly (paradoxical response) to benzos are the ones who will almost certainly respond to bumetanide, because GABA is working "in reverse". I do not think it says anything about glutamate.
DeleteWe have seen that some people have hypo and some hyper-active NMDAR signaling. I think the problem is with the receptors. Too much glutamate can be very damaging, but I do not think this is a what is happening in many people and not someone with a high IQ.
If your son still has a negative reaction to benzodiazepines, GABA is still working "in reverse". So I would go back to bumetanide rather than worry about glutamate.
For people with NMDAR dysfunction you either tune them up or down. This seems to work.
Petra,
DeleteIn one of my messages a while ago I linked a study about ASD which indeed showed that both hypo and hyper glutamate state can be present at the same time (different brain regions).
Im guessin that this is probably an impossible issue to fix of ASD, in other words if you was to take a nmda antagonist such as memantine you might lower the negative effects in some areas, but might also worsen the brain areas that were allready low in glutamate to start with.
I have used d-aspartic acid, it brings back some emotional intensity but also aggrevates other things such as irritability and headaches/neckpain.
Not to mention very vivid dreaming, where I would be half awake/half asleep at the same time in bed, getting maybe 4 hours of decent sleep @ max a night.
Maybe someone already posted this link on the Lactobacillus reuteri 6475 strain:
ReplyDeleteDiacylglycerol kinase synthesized by commensal Lactobacillus reuteri diminishes protein kinase C phosphorylation and histamine-mediated signaling in the mammalian intestinal epithelium.
https://www.ncbi.nlm.nih.gov/pubmed/28745328
"Collectively, the commensal microbe Lr may act as a "microbial antihistamine" by suppressing intestinal H1R-mediated proinflammatory responses via diminished pPKC-mediated mammalian cell signaling."
/Ling
A glimpse of hope regarding atcc 6475 possibly being released without dsm17938!:
ReplyDeleteLink was spotted by a sharp longecity user who recently posted it there about biogaia updating their facebook!:
https://www.facebook.com/BioGaia/posts/a-new-clinical-study-has-shown-that-biogaias-probiotic-strain-lactobacillus-reut/2629168633776061/